Putting a Stop on Pain: A Novel Nerve Cap Prevents Neuroma Formation
Erica B Lee, MS1, Aidan Weitzner, BS1, Bruce Enzmann, BS2, Anson Zhou, BME2, Ahmet Höke, MD, PhD2, Hai-Quan Mao, PhD2 and Sami H Tuffaha, MD3, 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
Purpose: Nerve injuries are common and can result from a vast array of mechanisms, including trauma and iatrogenic surgical injury. Painful growths of aberrant neural regeneration known as neuromas can be particularly challenging in the setting of amputation surgery as large caliber nerves are transected. Our group has previously developed a bioengineered funnel-shaped conduit to enhance targeted muscle reinnervation (TMR) outcomes for neuroma prevention through mechanical guidance and axonal inhibition by chondroitin sulfate proteoglycans (CSPGs). Given the success of this device, we sought to investigate the efficacy of a CSPG-incorporated nerve cap in preventing neuroma formation following nerve transection.
Methods: A cylindrical cap device composed of nonwoven poly-ε-caprolactone (PCL), was developed by electrospinning. The cap walls prevent intraneural macrophage infiltration and inflammation, which limits scarring and fibrosis at the nerve stump. Within the cap, CSPGs incorporated into a nanofiber hydrogel form an interpenetrating network to inhibit the regenerating axons. Using a rodent nerve injury model, we tested the effects of this device on neuroma formation and pain behaviors. Our groups included: (1) Sham, (2) Neuroma - sciatic nerve transection left in discontinuity, (3) Cap - sciatic nerve transection with a cap. Pain behaviors were observed on weekly basis until sacrifice at Week 24.
Results: By week 23, behavioral responses to mechanical stimulation of the coaptation site were significantly lower in the Cap animals as compared to Neuroma groups (p<0.0001), demonstrating successful prevention of neuroma formation. Cap animals were not significantly different than Sham animals in pain scores at Week 23. Upon preliminary histological analyses, cap animals demonstrate a lower expression of pain markers TRPV1 and substance P in the L3-L5 dorsal root ganglia as compared to neuroma animals. Qualitative histology of the cap device shows a progressive decline in axons from proximal to distal end of the nerve cap, indicating successful inhibition of regeneration.
Conclusions: Our findings suggest this CSPG-incorporated nerve cap successfully reduces neuroma formation and associated pain behaviors. Consequently, this device may present a simpler alternative to surgical techniques for neuroma prevention such as TMR. This cap is composed of FDA-approved materials that will facilitate clinical translation and presents a biologically compatible, non-invasive means by which we could optimize postoperative outcomes.
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